It is well documented that injured articular cartilage has only a limited ability for self-repair. Since articular cartilage is relatively avascular and aneural, loss of surface tissue will result in a permanently scarred site. Lesions which fracture subchondral bone, which has a greater vascular supply, will undergo an inflammation/repair response, with the damaged site filling with fibrocartilage tissue (Convery, et al. (1972) Clinical Orthopedics and Related Research 82:253-262). In either case, function is impaired and chronic pain is the usual prognosis, since the biochemical and biomechanical characteristics of the cartilage have been altered.
There are a number of different strategies that are used in cartilage repair. For example, microfracture, or Pridie drilling is often utilized. In this treatment, holes are created either by drilling or with a pick through the subchondral bone into the underlying cartilage. The holes allow stem cells from the bone marrow to enter the defect site and clot, and then form a repair tissue. This repair is generally found to result in a poor quality tissue, which breaks down with time.
Alternatively, surgeons have used Mosaicplasty™. In this technique, plugs of cartilage and bone are taken from the periphery of the joint and placed in the defect site. This technique has enjoyed some success, but is surgically very demanding and leaves donor tissue harvest sites which have some morbidity.
Autologous tissue engineering approaches have also been used in cartilage repair. For example, Carticel™ employs a commercial process to grow (culture) a patient's own (autologous) cartilage cells, known as chondrocytes, for use in treating damaged articular cartilage of the knee. Once the patient's cells are expanded in culture, they are reimplanted in the patient. The cells are held in place by a patch of periosteum, which is sutured in place, and then sealed to prevent cell migration using fibrin glue. This approach is very expensive, and is also surgically very demanding.
Other techniques for cartilage repair utilize growth factors and other signaling molecules. However, these techniques are still in the research phase, and have not been clinically proven.
Injectable, in situ polymerizing or crosslinking biomaterials have been used previously as defect-filling scaffolds for cartilage repair (Bryant, et al. J. Biomed Res., Jan. 1 2003, 64A(1), pp. 70-9; Temenoff, et al. J. Biomater. Sci. Polym Ed., 2003, 14(9), pp. 989-1004 and Sims, et al. Plast Reconstr., Surg., 1996, 98(5) pp. 843-50). These biomaterials are generally low viscosity, fluid-like solutions that permit mixing with cells and/or bioactive factors and may be polymerized or crosslinked in situ. While several in situ crosslinkable materials have been evaluated for cartilage repair in vivo, only a few have been prepared from natural biomaterials including collagens, chitosans, alginates, and hyaluronans (Lee, et al. Biomaterials, 2001, Chenite, et al. Biomaterials, 2000, 21(21) pp. 2155-61; Paige, et al. Plast Reconstr Surg, November 1995, 96(6) pp. 1390-8 and Nettles, et al. Ann Biomed Eng., March 2004, 32(3) pp. 391-7).
In prior work, biomaterials containing polypeptide sequences native to elastin have been shown to promote chondrocyte survival and cartilage matrix biosynthesis in vitro for primary chondrocytes, invertebral disc cells and for stem cells isolated from adipose tissue (Betre, et al. Biomacromolecules, September-October 2002, 3(5) pp. 910-6; Knight, et al. Trans. SFB, 2003; Betre, et al. Trans ORS, 2004). Elastin-based sequences may be crosslinked by multiple means, with evidence that the crosslinked systems do not interfere with chondrocyte survival and matrix deposition (Cappello, et al. J Control Release, 1998, 53(1-3) pp. 105-17, Cappello, Handbook of Biodegradable Polymers, 1997, Knight, et al Trans. SFB, 2003).
Synovial fluid in an injured joint is known to contain many factors which have an influence on the progression of osteoarthritis (see, for example, Fernandes, et al., “The Role of Cytokines in Osteoarthritis Pathophysiology”, Biorheology, 39 (1-2): 237-246, 2002). Cytokines, such as Interleukin-1 (IL-1) and Tumor Necrosis Factor-α (TNF-α), which are produced by activated synoviocytes, are known to upregulate matrix metalloproteinase (MMP) gene expression. Currently, research is aimed at finding biochemical agents that can neutralize this upregulation. Research is also being aimed at finding stimulatory agents to compensate for the deleterious effects of this upregulation. Such stimulatory agents include, for example, transforming growth factors (e.g., TGF-β) or insulin like growth factor (IGF-1).
The repair of cartilage defects is believed to be impaired by the same factors in synovial fluid as influence the degeneration of cartilage in osteoarthritis. In view of this, it would be advantageous to provide a cartilage repair technique, which involves producing a barrier against synovial fluid at the defect site. The barrier would seal the cartilage defect against synovial fluid and the deleterious factors therein. In this way, the healing wound could be temporarily protected.
It would also be advantageous if the use of a barrier against synovial fluid had application in all synovial joint tissues. For example, migration of synovial fluid into the tunnel of cruciate ligament grafts has been implicated in the post surgery tunnel widening phenomena which is observed. In view of this, it would be advantageous to provide a ligament grafting technique, which involves producing a barrier against synovial fluid ingress into the bone tunnels. The barrier would seal the bone tunnels against synovial fluid and the deleterious factors therein.
It is currently not possible to effectively repair torn ligaments that are within the synovial capsule. It is likely that a factor responsible for this is the influence of synovial fluid, and the factors within it, on the healing process. Therefore, there is a need for an improved method of repairing torn or damaged ligaments, which involves creating a barrier between the damaged ligament and the synovial fluid.